Antituberculosis Therapy–Induced Acute Liver Failure: Magnitude, Profile, Prognosis, and Predictors of Outcome

Abstract

Antituberculosis therapy (ATT)–associated acute liver failure (ATT-ALF) is the commonest drug-induced ALF in South Asia. Prospective studies on ATT-ALF are lacking. The current study prospectively evaluated the magnitude, clinical course, outcome, and prognostic factors in ATT-ALF. From January 1986 to January 2009, 1223 consecutive ALF patients were evaluated: ATT alone was the cause in 70 (5.7%) patients. Another 15 (1.2%) had ATT and simultaneous hepatitis virus infection. In 44 (62.8%) patients, ATT was prescribed empirically without definitive evidence of tuberculosis. ATT-ALF patients were younger (32.87 [±15.8] years), and 49 (70%) of them were women. Most had hyperacute presentation; the median icterus encephalopathy interval was 4.5 (0-30) days. The median duration of ATT before ALF was 30 (7-350) days. At presentation, advanced encephalopathy and cerebral edema were present in 51 (76%) and 29 (41.4%) patients, respectively. Gastrointestinal bleed, seizures, infection, and acute renal failure were documented in seven (10%), five (7.1%), 26 (37.1%), and seven (10%) patients, respectively. Compared with hepatitis E virus (HEV) and non-A non-E–induced ALF, ATT-ALF patients had nearly similar presentations except for older age and less elevation of liver enzymes. The mortality rate among patients with ATT-ALF was high (67.1%, n = 47), and only 23 (32.9%) patients recovered with medical treatment. In multivariate analysis, three factors independently predicted mortality: serum bilirubin (≥10.8 mg/dL), prothrombin time (PT) prolongation (≥26 seconds), and grade III/IV encephalopathy at presentation. Conclusion: ATT-ALF constituted 5.7% of ALF at our center and had a high mortality rate. Because the mortality rate is so high, determining which factors are predictors is less important. A high proportion of patients had consumed ATT empirically, which could have been prevented. Hepatology 2010

An Update on Drug-induced Liver Injury

“…9 DILI is a leading cause of acute liver failure (ALF) in the Western world, with paracetamol being the commonest drug followed by antimicrobials. 12,13 In India antituberculosis drugs are the commonest cause of druginduced ALF in adults and children, [14][15][16] contributing to 5.7-22% of all cases of ALF. [14][15][16] Paradoxically, many could be preventable, as empirical treatment for tuberculosis in 43-60% drives most of the reasons for antituberculous ALF.…”

“…12,13 In India antituberculosis drugs are the commonest cause of druginduced ALF in adults and children, [14][15][16] contributing to 5.7-22% of all cases of ALF. [14][15][16] Paradoxically, many could be preventable, as empirical treatment for tuberculosis in 43-60% drives most of the reasons for antituberculous ALF. 14,17 A brief summary of drugs causing hepatotoxicity and other demographic characteristics are depicted in Table 1.…”

“…[14][15][16] Paradoxically, many could be preventable, as empirical treatment for tuberculosis in 43-60% drives most of the reasons for antituberculous ALF. 14,17 A brief summary of drugs causing hepatotoxicity and other demographic characteristics are depicted in Table 1. 9,[18][19][20][21] …”

Approach to Clinical Syndrome of Jaundice and Encephalopathy in Tropics

“…17 None of the patients who were diagnosed as ALF on the basis of clinical presentation with jaundice, encephalopathy and coagulopathy, on postmortem liver biopsies showed evidence of underlying chronic liver disease.…”

“…There are relatively few druginduced cases except those caused by ATTs. 17 In Australia, Paracetamol (Acetaminophen) overdose was seen in 36% cases while Viral hepatitis was seen in only 14%. Additional 34% were classified as non-A, non-B viral hepatitis.…”